Safety and Efficacy of Donafenib in Patients With Advanced Hepatocellular Carcinoma

Donafenib in Advanced Hepatocellular Carcinoma: A Randomized Phase 1B Study of Safety, Efficacy, and Pharmacokinetics

This phase IB study of donafenib, an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases, is to assess toxicity,efficacy and pharmacokinetics in patients wiht advanced hepatocellular carcinoma (HCC) .

Study Overview

• Status: Completed
• Conditions: HCC
• Intervention / Treatment: Drug: Donafenib(200mg); Drug: Donafenib(300mg)

Detailed Description

Eligibility Criteria:

• 18 -70 years old;
• Patients with measurable, histologically proven, inoperable HCC;
• Child-Pugh (CP) score of A;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less.
• Patients received prior systemic treatments for HCC before 4 weeks;
• Patients received operate before 3 months;
• Patients received TACE before 4 weeks;
• Life expectancy at least 3 months;
• Adequate hepatic and renal function;
• Adequate hematologic function (platelet count,≥70×109per liter;hemoglobin ≥8.5 g per deciliter);
• Prothrombin time international normalized ratio≤2; or prothrombin time ≤16 seconds;or APTT≤43s;or TT≤21s.

Exclusion Criteria:

• Patients had prior treatment with sorafenib;
• CNS involvement.

Method:

• open-label,randomized,multiceters study;
• 2 dose cohorts: 200mg bid and 300mg bid;
• Patients with advanced HCC(inoperable) and Child-Pugh (CP) A , randomized,receive continuous donafenib either 200mg bid or 300mg bid in 4 weeks cycles;
• Sample size:106 patients(53 patients in each dose cohort).

Endpoints:

• Safety: toxicities are assessed according to CTCAE 3.0;
• TTP:Tumor response is assessed every two cycles using RECISIT1.1 criteria;
• Donafenib pharmacokinetics is measured in plasma samples.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital,SCU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 -70 years old
• Patients with measurable, histologically proven, inoperable HCC
• Child-Pugh (CP) score of A
• Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less.
• Patients received prior systemic treatments for HCC before 4 weeks
• Patients received operate before 3 months
• Patients received TACE before 4 weeks
• Life expectancy at least 3 months
• Adequate hepatic and renal function
• Adequate hematologic function (platelet count,≥70×109per liter;hemoglobin ≥8.5 g per deciliter)
• Prothrombin time international normalized ratio≤2; or prothrombin time ≤16 seconds;or APTT≤43s;or TT≤21s.

Exclusion Criteria:

• Patients had prior treatment with sorafenib
• CNS involvement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Donafenib(200mg); Donafenib 200 mg orally twice daily,each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.	Drug: Donafenib(200mg); Donafenib 200mg,bid,po; Other Names: A Group
Active Comparator: Donafenib(300mg); Donafenib 300 mg orally twice daily,each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.	Drug: Donafenib(300mg); Donafenib 300mg,bid,po; Other Names: B Group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Patient visits are scheduled every 4 weeks to monitor safety and drug accountability. Patients were monitored for adverse events by use of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0	1 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression(TTP)	Patient visits are scheduled every 8 weeks to monitor efficacy.TTP is measured from the date of randomisation until disease progression according to RECIST 1.1.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to symptomatic progression(TTSP)	Symtomatic progression is measured with the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-HP) domain of physical wellbeing and additional concerns at baseline and every 4 weeks.TTSP is measured from the date of randomisation until symptomatic progression.	1 year

Collaborators and Investigators

• Sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
• Collaborators: Tigermed Consulting Co., Ltd
• Investigators: Principal Investigator: Feng Bi, Doctor, Sichuan University

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): October 30, 2016

Study Registration Dates

• First Submitted: August 26, 2014
• First Submitted That Met QC Criteria: August 27, 2014
• First Posted (Estimate): August 29, 2014

Study Record Updates

• Last Update Posted (Actual): March 22, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: HCC; Advanced; Donafenib; inoperable; Phase 1B
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular
• Other Study ID Numbers: ZGDH1B

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No